Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell Metab. 2012 Jun 6;15(6):827-37. doi: 10.1016/j.cmet.2012.05.001.
Dysregulated metabolism is a hallmark of cancer cell lines, but little is known about the fate of glucose and other nutrients in tumors growing in their native microenvironment. To study tumor metabolism in vivo, we used an orthotopic mouse model of primary human glioblastoma (GBM). We infused (13)C-labeled nutrients into mice bearing three independent GBM lines, each with a distinct set of mutations. All three lines displayed glycolysis, as expected for aggressive tumors. They also displayed unexpected metabolic complexity, oxidizing glucose via pyruvate dehydrogenase and the citric acid cycle, and using glucose to supply anaplerosis and other biosynthetic activities. Comparing the tumors to surrounding brain revealed obvious metabolic differences, notably the accumulation of a large glutamine pool within the tumors. Many of these same activities were conserved in cells cultured ex vivo from the tumors. Thus GBM cells utilize mitochondrial glucose oxidation during aggressive tumor growth in vivo.
代谢失调是癌细胞系的一个标志，但对于在其天然微环境中生长的肿瘤中葡萄糖和其他营养物质的命运知之甚少。为了研究体内肿瘤代谢，我们使用了原发性人胶质母细胞瘤（GBM）的原位小鼠模型。我们将（13）C 标记的营养物质注入携带三种独立 GBM 系的小鼠中，每种系都有一组不同的突变。所有三种系都表现出糖酵解，这是侵袭性肿瘤的预期表现。它们还表现出出乎意料的代谢复杂性，通过丙酮酸脱氢酶和柠檬酸循环氧化葡萄糖，并利用葡萄糖提供氨甲酰磷酸和其他生物合成活性。将肿瘤与周围大脑进行比较显示出明显的代谢差异，特别是肿瘤内积累了大量谷氨酰胺池。这些相同的活性在从肿瘤体外培养的细胞中也得到了保留。因此，GBM 细胞在体内侵袭性肿瘤生长过程中利用线粒体葡萄糖氧化。
